METTL16 Inhibits Lens Epithelial Cells Function in Diabetic Cataract via m6A-Modified DKK1-Mediated Wnt/β-Catenin Signaling

Sep 30, 2026

Explores how methyltransferase-like protein 16 (METTL16) and m6A RNA methylation contribute to diabetic cataract progression by linking METTL16 to Dickkopf-1 (DKK1) and Wnt/β-catenin signaling. m6A levels in diabetic cataract anterior capsule tissue and high-glucose (HG)-treated human lens epithelial cells (HLECs) were assessed, alongside METTL16 expression. MeRIP, RNA stability, and functional assays showed METTL16 and m6A were elevated, DKK1 increased with METTL16, and DKK1 negatively associated with β-catenin nuclear translocation, regulating proliferation, migration, and cell-cycle progression. DKK1 inhibition reduced HG-induced lens opacity.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Lens METTL16 Inhibits Lens Epithelial Cells Function in Diabetic Cataract via m6A-Modified DKK1-Mediated Wnt/β-Catenin Signaling Bei Zhang,1 ,2 Yahui Sun,1 ,2 Xiaohui Jiang,1 ,2 Zhixuan Hu,1 ,2 Xue Wang,1 ,2 and Yun-e Zhao1 ,2 1Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China 2National Clinical Research Center for Ocular Diseases, State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China Correspondence: Yun-e Zhao, Eye Hospital at Hangzhou, Wenzhou Medical University, 270 West Xueyuan Road, Wenzhou 325027, Zhejiang, China; [zye@mail.eye.ac.cn](zye@mail.eye.ac.cn); [zyehzeye@126.com](zyehzeye@126.com). BZ, YS, and XJ contributed equally to the work presented here and should therefore be regarded as equivalent authors. Received: October 11, 2025 Accepted: December 9, 2025 Published: January 5, 2026 Citation: Zhang B, Sun Y, Jiang X, Hu Z, Wang X, Zhao Y. METTL16 inhibits lens epithelial cells function in diabetic cataract via m6A-modified DKK1-mediated Wnt/β-catenin signaling. Invest Ophthalmol Vis Sci. 2026;67(1):1 . [https://doi.org/10.1167/iovs.67.1.1](https://doi.org/10.1167/iovs.67.1.1) PURPOSE. To explore the role of methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) methyltransferase, in the development and progression of diabetic cataracts (DCs), as its underlying molecular mechanisms remain unknown. METHODS. We evaluated m6A methylation levels in total RNA isolated from DC anterior capsule tissue and high glucose (HG)-induced human lens epithelial cells (HLECs) using m6A quantification and dot blot analysis. The expression levels of METTL16 in the anterior capsule tissue were detected using western blot analysis. Methylated RNA immunoprecipitation (MeRIP), RNA stability assays, and other relevant experiments were performed to investigate the regulatory mechanisms of METTL16 on methylation levels in HLECs. Additionally, cellular functions including proliferation, migration, and cell-cycle progression were assessed. RESULTS. The expression level of METTL16 and the level of m6A methylation were highly elevated in the DC anterior capsule tissue and HG-induced HLECs. MeRIP analysis revealed that Dickkopf-1 (DKK1) might act as the target of METTL16 via the Wnt/β-catenin pathway. Notably, the expression of DKK1 increased with the increase in METTL16 expression in HG-induced HLECs. Furthermore, DKK1 expression was negatively correlated with the nuclear translocation of β-catenin, thereby regulating cell proliferation, migration, and cell-cycle progression in HLECs. In addition, HG-induced lens opacity contributes to cataract formation, and treatment with the DKK1 inhibitor WAY- 262611 effectively prevented the development of this pathological process. CONCLUSIONS. The METTL16–DKK1–Wnt/β-catenin axis inhibits the proliferation, migration, and cell-cycle progression of HG-induced HLECs. These findings provide an epigenetic insight into the pathogenesis of DC. Keywords: diabetic cataract, METTL16, DKK1, Wnt/β-catenin signaling D iabetes is one of the leading causes of death and disability worldwide and affects people regardless of country, age group, or sex.1 International Diabetes Federation projections show that one in eight adults—approximately 783 million people—will be living with diabetes by 2045, an increase of 46% .2 The incidence of diabetic cataracts (DCs) has been on the rise in tandem with the continuous growth in the number of individuals suffering from type 2 diabetes. DC is characterized by the disruption of lens optical transparency due to activation of the polyol pathway,3 oxidative stress,4 and accumulation of advanced glycation end products in a continuously chronic hyperglycemic environment.5 ,6 The current treatment for DC is phacoemulsification cataract aspiration combined with intraocular lens implantation. Patients with diabetes represent a higher risk population

FAQs

What is the main goal of this study on diabetic cataract?

To determine the role of METTL16 in diabetic cataract development and progression and to clarify the underlying molecular mechanism involving m6A modification and signaling through DKK1 and Wnt/β-catenin.

How were METTL16, m6A, and DKK1 investigated in diabetic cataract tissue and cells?

m6A methylation levels were measured in diabetic cataract anterior capsule tissue and in high-glucose-induced HLECs; METTL16 expression was assessed by western blot. MeRIP, RNA stability assays, and related experiments were used to study regulatory mechanisms, followed by cellular functional assays.

What effect does DKK1 have on β-catenin signaling and HLEC behaviors under high glucose?

DKK1 expression negatively correlates with nuclear translocation of β-catenin, and this axis regulates HLEC proliferation, migration, and cell-cycle progression under high-glucose conditions.

Sep 30, 2026

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